1. Field of the Invention
The present invention relates generally to the field of molecular biology and immunology. More particularly, it concerns molecular antibody design and antibody-based reagents and therapeutics.
2. Description of Related Art
Antibody therapeutics have a dominant market share in the treatment of cancers and other human diseases with estimated sales exceeding USD $56 billion in 2011. Antibodies kill cancer cells in part by engaging and activating immune cells. One important mechanism underlying the potency of antibody therapeutics is the ability of antibody to recruit immune cells to a target antigen (or cell). Thus, the Fc region of an antibody is crucial for recruitment of immunological cells and antibody dependent cytotoxicity (ADCC). In particular, the nature of the ADCC response elicited by antibodies depends on the interaction of the Fc region with receptors (FcRs) located on the surface of many cell types. Humans contain five different classes of Fc receptors. In addition haplotypes, or genetic variants of different FcRs belonging to a particular class are known. The binding of an antibody to FcRs determines its ability to recruit other immunological cells and the type of cell recruited. Hence, the ability to engineer antibodies that can recruit only certain kinds of cells can be critically important for therapy.
Currently, all antibody therapeutics are of the IgG subclass. Therapeutic IgG antibodies engage the Fcγ class of receptors via Fc domain interaction on the surface of various blood cells which in turn become activated to kill tumor cells. For some therapeutics efficacy could be improved by the additional recruitment of cells that display Fcα or Fcα receptors. However, to date, antibody Fc polypeptides have not been identified that can bind to additional Fc receptors.